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Hui Lin, Siva Pramodh Kambhampati, Rangaramanujam Kannan, Samuel C Yiu; Dendrimer-based anti-inflammatory therapy for induced autoimmune dacryoadenitis in a rabbit model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5687.
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© ARVO (1962-2015); The Authors (2016-present)
Dendrimer is known to enhance anti-inflammatory efficacy in several diseases. Sjogren’s syndrome, a severe form of dry eye, is characterized by the presence of lymphocytes infiltration in lacrimal gland (LG) which release soluble proinflammatory mediators. Therapies that can target and deliver anti-inflammatory drugs to immune effector cells will be beneficial. The purpose of this study is to investigate: a) the dendrimer distribution in LG of rabbits with induced autoimmune dacryoadentis and, b) evaluate the potential of dendrimer–drug therapy.
Autoimmune dacryoadentis was induced in New Zealand White rabbits by injecting autologous peripheral blood lymphocytes, which had been activated in a mixed cell reaction with acinar cells isolated from right inferior LG, back into the donor animals remaining left inferior LG. Animals with established disease were treated with dendrimer-Cy5 (D-Cy5), dendrimer-dexamethasone (D-Dex) or dexamethasone (Dex) alone by subconjunctival injection. Healthy animals (Sham-injection during model establishment) received subconjunctival injection of D-Cy5 as well. Intravenous injection of D-Cy5 was also performed in diseased model. LGs were harvested 24hrs, 72hrs and 2 weeks after treatment and prepared for section staining and RNA extraction. Immunostaining and real-time PCR for CD18, RTLA and IBA1 were performed to evaluate inflammatory cells infiltration.
Upon subconjunctival administration, D-Cy5 was selectively localized and retained in the lymphocytes, acinar cells and extracellular matrix in LG in the established disease model from 24 hrs to 2 weeks. Minimal D-Cy5 uptake was found in Sham group animals. Co-localization of D-Cy5 and IBA1 staining was found in intravenous injection group. Compared to Dex group, D-Dex group has significant less amount of inflammatory cell infiltration.
Dendrimer nanoparticle mediated delivery might serve as a good treatment options for enhanced intracellular delivery and efficacy of drugs to target cells in LG and has its potential clinical application for autoimmune LG diseases as Sjogren’s syndrome.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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